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Updated: Mar 19, 2026
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Left Atrial Volume Index and Left Ventricular Mass Index Determine the Benefits of Spironolactone in Patients With
Hongbin Zang1, Chenhong Jia1, Yilong Pan1
1Department of Cardiology Shengjing Hospital of China Medical University Shenyang China.
Insights
Spironolactone benefits patients with heart failure with preserved ejection fraction (HFpEF) by reducing cardiovascular mortality and hospitalizations. These benefits are linked to specific cardiac structural and functional parameters, particularly increased left atrial volume index or left ventricular mass index.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The efficacy of spironolactone in heart failure with preserved ejection fraction (HFpEF) based on cardiac structure or function remains unclear.
- HFpEF is characterized by preserved left ventricular ejection fraction (LVEF) but impaired diastolic function or elevated filling pressures.
Purpose of the Study:
- To investigate the response of HFpEF patients to spironolactone based on cardiac structure and function.
- To identify specific patient subgroups within HFpEF who benefit most from spironolactone treatment.
Main Methods:
- Post hoc analysis of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial).
- Included 757 participants with LVEF ≥50% and evidence of abnormal LV diastolic function or filling pressures.
- Stratification based on cardiac structure (left atrial volume index, LV mass index) and function, using log-rank tests and Cox regression models.
Main Results:
- Spironolactone reduced cardiovascular mortality in patients with increased left atrial volume index (adjusted HR, 0.48).
- Spironolactone decreased heart failure hospitalization and a composite outcome in patients with increased LV mass index (adjusted HRs 0.51 and 0.63, respectively).
- In patients with both increased left atrial volume index and LV mass index, spironolactone significantly reduced cardiovascular mortality, heart failure hospitalization, and the composite outcome (adjusted HRs 0.31, 0.26, and 0.33, respectively).
Conclusions:
- Spironolactone demonstrates significant benefits in HFpEF patients with specific cardiac structural abnormalities.
- Treatment with spironolactone can reduce cardiovascular mortality and heart failure hospitalizations in selected HFpEF populations.
- Cardiac structure, specifically left atrial volume index and LV mass index, can predict response to spironolactone in HFpEF.
Background:
It is unclear whether patients with heart failure with preserved ejection fraction respond to spironolactone based on cardiac structure or function.
Methods:
A post hoc analysis was performed among participants with left ventricular (LV) ejection fraction ≥50% and evidence of abnormal LV diastolic function or filling pressures in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial). Log-rank tests and Cox regression models were used for comparison between groups.
Results:
Totally, 757 subjects were qualified and stratified by parameters on cardiac structure or function. In patients with increased left atrial volume index, spironolactone reduced cardiovascular mortality (adjusted hazard ratio [HR], 0.48 [95% CI, 0.24-0.98]; P=0.042, log-rank; interaction P=0.045). Meanwhile, in patients with increased LV mass index, spironolactone decreased heart failure hospitalization (adjusted HR, 0.51 [95% CI, 0.32-0.80]; P=0.009, log-rank; interaction P=0.041) and the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death (adjusted HR, 0.63 [95% CI, 0.43-0.93]; P=0.045, log-rank; interaction P=0.029). Then, in participants with increased left atrial volume index and LV mass index, who matched at 1:1 ration by propensity score matching, spironolactone reduced cardiovascular mortality (adjusted HR, 0.31 [95% CI, 0.11-0.92]; P=0.039, log-rank), heart failure hospitalization (adjusted HR, 0.26 [95% CI, 0.10-0.68]; P=0.005, log-rank), and the composite outcome (adjusted HR, 0.33 [95% CI, 0.15-0.72]; P=0.006, log-rank).
Conclusions:
Spironolactone reduced cardiovascular mortality, heart failure hospitalization, or the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death in patients with heart failure with preserved ejection fraction with increased left atrial volume index or LV mass index.
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